DHRS2 (dehydrogenase/reductase 2) is an NADPH-dependent oxidoreductase belonging to the short-chain dehydrogenase/reductase (SDR) superfamily 1. Its primary function is catalyzing reduction of dicarbonyl compounds, functioning as a carbonyl reductase in detoxification of reactive carbonyl compounds 2. DHRS2 also displays minor hydroxysteroid dehydrogenase activity toward bile acids but lacks activity with retinoids and sugars 2. Mechanistically, DHRS2 stabilizes p53 by attenuating MDM2-mediated degradation, leading to increased p53 transcriptional activity and accumulation of p21 3. In cancer cells, DHRS2 suppresses proliferation and migration while reducing reactive oxygen species production 4. Recent studies reveal DHRS2 inhibits ovarian cancer growth by downregulating choline kinase α to disrupt choline metabolism 5, and functions in a SIRT3-DHRS2 axis that preserves mitochondrial homeostasis in vascular endothelial cells 6. Clinically, DHRS2 expression is repressed in prostate cancer and T-cell acute lymphoblastic leukemia, functioning as a tumor suppressor 78. Additionally, DHRS2 associates with β-cell sensitivity to lipotoxicity in type 2 diabetes 9. DHRS2 represents a promising therapeutic target for cancer and metabolic diseases through modulation of redox homeostasis and lipid metabolism reprogramming.